Determination of the Single Nucleotide Polymorphisms C3435 and G2677T in MDR1 and C421A in BCRP in blood samples of patients with inflammatory bowel disease and healthy controls in the swiss population

Abstract

Aims: P-glycoprotein (P-gp, ABCB1, MDR1) and breast cancer resistance protein (BCRP, ABCG2) protect the luminal cells of the gastro-intestinal tract from potentially toxic substances. Genetic polymorphisms have previously been associated with disease susceptibility, severity, and treatment prognosis of inflammatory bowel disease. We investigated the prevalence of frequent single nucleotide polymorphisms of P-gp and BCRP in the Swiss population in healthy volunteers (n = 17) and patients newly diagnosed with Crohn’s Disease (CD, n = 34) or Ulcerative Colitis (UC, n = 38).
Methods: DNA from peripheral blood cells was used to assess genotype and allele frequencies of MDR1 C3435T, MDR1 G2677T, and BCRP C421A.
Results: Weak associations for BCRP C421A (p < 0.18) and MDR1 G2677T (p < 0.27) were seen in UC and a trend towards the wild type allele for MDR1 C3435T (p < 0.46). MDR1 3435CC / BCRP 421CC (Χ2: 1.0142, p < 0.30) in UC and MDR1 2677G / BCRP 421A (Χ2: 1.5615, p < 0.22) also weakly correlated with UC. Results for BCRP C421A in particular justify further study.
Conclusions: Trends towards certain alleles and haplotypes were seen. These merit further studies in larger subgroups (e.g. by disease stage, therapy refractory patients, etc.).